Variant X-48981820-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020137.5(GRIPAP1):c.1652G>A(p.Arg551Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,062,236 control chromosomes in the GnomAD database, including 1 homozygotes. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000075 ( 1 hom. 2 hem. )

Consequence

GRIPAP1
NM_020137.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.806

Variant links:

Genes affected

GRIPAP1 (HGNC:18706): (GRIP1 associated protein 1) This gene encodes a guanine nucleotide exchange factor for the Ras family of small G proteins (RasGEF). The encoded protein interacts in a complex with glutamate receptor interacting protein 1 (GRIP1) and plays a role in the regulation of AMPA receptor function. [provided by RefSeq, Aug 2013]

GRIPAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06092587).

BP6

Variant X-48981820-C-T is Benign according to our data. Variant chrX-48981820-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3102581.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIPAP1	NM_020137.5 linkuse as main transcript	c.1652G>A	p.Arg551Gln	missense_variant	18/26	ENST00000376423.8	NP_064522.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIPAP1	ENST00000376423.8 linkuse as main transcript	c.1652G>A	p.Arg551Gln	missense_variant	18/26	1	NM_020137.5	ENSP00000365606	P3	Q4V328-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1062236

Hom.:

Cov.:

AF XY:

0.00000583

AC XY:

AN XY:

342780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000608

Gnomad4 OTH exome

AF:

0.0000670

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000175

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.92

DANN

Benign

0.95

DEOGEN2

Benign

0.0052

.;T;T

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

.;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.23

Sift4G

Benign

0.91

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.074

MutPred

0.11

.;.;Loss of helix (P = 0.0068);

MVP

0.32

ClinPred

0.18

GERP RS

-7.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.040

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over